The process of spray drying has been widely used in the production of pharmaceuticals since the 1940s (Corrigan, 1995). The food industry also commonly employs spray drying to produce food products demonstrating enhanced stability and suitable for long term storage (Sliwinski et al., 2004). Spray drying is a one step process used to convert a liquid based feedstock (such as a solution, suspension or emulsion) into a dried powder form by atomizing the feedstock in droplets, into a hot drying-medium, typically air or nitrogen. The process provides enhanced control over particle size, size distribution, particle shape, density, purity and structure. As formulators are able to control these parameters so precisely, spray drying as a possible method for formulating dry powder compositions intended for pulmonary delivery has also been investigated in recent years (WO 96/32149).
Spray drying active pharmaceutical ingredients (API) or biological material suitable for inhalation normally requires the presence of stabilizing excipients and/or diluents.
The de-facto spray drying excipient of choice is often Mannitol as it possesses many advantageous properties. Mannitol will readily dry in a crystalline state, is water soluble and is considered non-hygroscopic as it picks up less than 1% moisture at relative humidity as high as 70% (Handbook of Pharmaceutical Excipients, 6th Edition, R. C. Rowe). In addition it can pick up 10% of mass in water at humidity's >70% RH. However despite mannitol's attractive stabilizing capabilities, it is a tussive agent and will induce coughing when administered via the pulmonary route.
As an alternative choice excipient, trehalose is often used for spray drying compositions. Trehalose (α-D-glucopyranosyl-α-D-glucopyranoside) is a naturally occurring, non-reducing disaccharide which was initially found to be associated with the prevention of desiccation damage in certain plants and animals which can dry out without damage and can revive when rehydrated. Trehalose however does not spray dry completely crystalline and will instead form an amorphous matrix. This amorphous matrix is hygroscopic and will readily absorb water. Spray-dried trehalose therefore suffers from physical stability issues, principally particle agglomeration, resulting in loss of primary particle size and aerosol performance characteristics.
Thus a need still exists for materials such as excipients for preparing stable inhalable compositions which exhibit excellent aerosolisation properties and demonstrate very low levels of agglomeration. Ideally, such excipients will spray dry in a crystalline form and will possess various favourable attributes such as low toxicity (with no cough induced side effects), low hygroscopicity, high melting point, with very low moisture content (advantageous for long term storage).